Use of transfected Drosophila S2 cells to study NK cell activation

Determining the contribution of individual receptors to natural killer (NK) cell function is complicated by the multiplicity of activating and inhibitory NK cell receptors. Mammalian target cells typically express a variety of ligands for NK cell receptors. Engagement of NK cell receptors by antibodies may not mimic activation by natural ligands. To define requirements for activation and dissect the contribution of receptors to NK cell function, we have generated Drosophila Schneider line 2 (S2) cell transfectants expressing ligands for NK cell receptors. The evolutionary distance between Drosophila and mammals greatly reduces the potential of recognition of insect cell molecules by mammalian NK cells. Here, we present methods for maintenance and transfection of S2 cells, as well as protocols for their use in NK cell assays.